pancreatic insufficiency and high concentrations of sodium chloride in 
sweat, the pulmonary manifestations are, by far, the most common life 
threatening aspects of the disease. The earliest observed morphologic 
lesions are mucous obstruction of small airways and inflammation of the 
bronchiolar walls (Bedrossian et al., 1976). Bronchoalveolar lavage studies 
demonstrate neutrophil -dominated inflammation in airway epithelial lining 
fluid of infants with CF as early as age 1 (Birrer et al . , submitted for 
publication). As the disease progresses, there is inflammation of large and 
small airways, hypertrophy of submucosal glands, and a general increase in 
the numbers of secretory cells. There is obstruction of airways with mu- 
cous. Chronic infection of the airways develops, with accompanying acute 
and chronic inflammation. With increasing cycles of mucous obstruction, 
infection and inflammation, the airways become damaged, culminating in 
bronchiectasis. Although the disease is primarily based in the airways, the 
mucus obstruction, inflammation and infection commonly extends to the peri- 
bronchiolar alveolar structures, causing fibrosis and alveolar destruction. 
In the late stages of the disease, the lung is markedly deranged with 
dilated and sometimes stenosed airways, emphysema, and peribronchiolar and 
interstitial alveolar inflammation and fibrosis (Bedrossian et al., 1976). 
Infection plays a prominent role in the pathogenesis of the derangements of 
the lung in CF. The infection is primarily endobronchial and is chronic, 
with acute exacerbations. The most common organisms involved are Hemophilus 
influenza . Staphylococcus aureus . and Pseudomonas aeruginosa . The fact that 
the infection is confined to the lung argues strongly that the host defense 
problems permitting the infection are local rather than systemic (Elborn 
and Shale, 1990; Kulczycki et al., 1978). The pathobiologic processes per- 
mitting chronic infection of the airways are not fully understood, but may 
involve abnormalities in the volume, physical properties and/or charac- 
teristics of mucus in the respiratory tract (Hubbard et al., 1992). In 
addition, the dysfunctional and/or damaged airway epithelial cells may 
permit organisms such as P. aeruginosa to adhere to the epithelium, permit- 
ting chronic colonization (Woods et al., 1980). 
Concomitant with the infection is chronic intense inflammation of the air- 
ways that is dominated by neutrophils. Mononuclear phagocytes and lympho- 
cytes play a lesser role. Sputum and lavage fluid analyses of CF patients 
reveal large concentrations of inflammatory mediators, particularly neutro- 
phil proteases (McElvaney et al . , 1991 ). Bacterial proteases, including 
Pseudomonas elastase are present, but to a far lesser extent (Doring et 
al., 1989). Concomitant with the response to the infection, inflammatory 
cells in the local milieu are chronically releasing large amounts of oxi- 
dants (Roum et al . , 1990). Together, the mediators released by the inflam- 
matory cells overwhelm the normal anti-inflammatory defense screen of the 
epithelial surface, and interfere with local host defense processes in the 
airways (McElvaney et al . , 1991; Roum et al . , 1990). The inflammatory 
mediators also exaggerate epithelial cell secretion (Sommerhoff et al . , 
1990) , thus perpetuating the increased mucus production that characterizes 
the disease. Consequent to this chronic, overwhelming inflammation, there 
is progressive damage to the epithelium culminating in the bronchiectasis 
and other permanent derangements of the lung that characterize CF. 
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